The Pathogenic Mechanisms of GBA1-Associated Parkinson's and their Mitigation by Small Molecule Inhibitors
Full Grant 2024-2025 | Prof. Miguel Weil | Prof. Daniel Segal
Mutations in the GBA1 gene are a major risk factor for development of Parkinson’s disease (PD). This is rather enigmatic since GBA1 is associated with another disease, namely Gaucher disease.
The underlining mechanism linking GBA1 to PD remains unclear. Our recently published findings show that the metabolite which accumulates due to GBA1 mutations can promote aggregation of α-Synuclein, the culprit of PD.
We have shown this in the test tube, and our preliminary experiments indicate that this happens also in patient cells of GBA1-associated PD.
These findings suggest a novel target for treatment of GBA1-associated PD. Indeed, our preliminary results indicate that certain small molecules are capable of inhibiting the GBA1- associated aggregation of α-Synuclein, hence may provide leads for development of novel therapeutics.
In the present proposal we aim at identifying the cellular processes that go awry in GBA1-associated PD, and examine how the small molecules ameliorate them.
